This research is based on the long-term observation that hyaline cartilage is a connective tissue that lacks a capillary blood supply and is only rarely invaded by neoplasms. We were able to isolate from cartilage a spectrum of low molecular weight proteins, which we have functionally defined as Anti-Invasion Factor (AIF). One aspect of the invasion process is the elaboration of proteases, which act on components in the extracellular matrix of the host tissue. At least some of the anti-invasion properties of AIF are due to the presence of protease inhibitors that act on tumor proteases. AIF also contains an inhibitor of proliferation that is selectively active on endothelial cells. We are in the process of fractionating AIF and attempting to isolate and identify its active principles with respect to protease inhibitors and antiproliferative activities. Major emphasis is currently directed towards the isolation of pure matrix-degrading enzymes (e.g., elastase) and the study of the interaction of these enzymes with the AIF-derived inhibitors. In addition, a culture system of chondrocytes will be utilized to examine the interaction between chondrocytes and tumor cells. (J)